Macrophage Polarization Induced by Bacteria‐Responsive Antibiotic‐Loaded Nanozymes for Multidrug Resistance‐Bacterial Infections Management

Abstract Inherited bacterial resistance and biofilm‐induced local immune inactivation are important factors in the failure of antibiotics to fight against bacterial infections. Herein, antibiotic‐loaded mesoporous nanozymes (HA@MRuO 2 ‐Cip/GOx) are fabricated for overcoming bacterial resistance, and activating the local immunosuppression in biofilm microenvironment (BME). HA@MRuO 2 ‐Cip/GOx are prepared by physical adsorption between ciprofloxacin (Cip) or glucose oxidase (GOx) and MRuO 2 NPs, and modified with hyaluronic acid (HA). In vitro, HA@MRuO 2 ‐Cip/GOx cleaves extracellular DNA (eDNA) to disrupt biofilm, thereby enhancing Cip kill planktonic bacteria. Furthermore, HA@MRuO 2 ‐Cip/GOx can induce polarization and enhance phagocytosis of a macrophage‐derived cell line. More importantly, in vivo therapeutic performance confirms that HA@MRuO 2 ‐Cip/GOx can trigger macrophage‐related immunity, and effectively alleviate MRSA‐bacterial lung infections. Accordingly, nanocatalytic therapy combined with targeted delivery of antibiotics could enhance the treatment of bacterial infections.